With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Objective:To investigate the effects of multimodal and multisensory stimulation training on feeding-swallowing and neurological functions in stroke patients with dysphagia.Methods:Stroke patients with dysphagia treated at Henan Provincial People's Hospital from January 2023 to October 2024 were enrolled. Patients were randomly divided into three groups according to the random number table method, with 36 patients in each group. These three groups underwent different interventions for a period of 8 weeks: multisensory stimulation intervention (stimulation group), multimodal rehabilitation training intervention (rehabilitation group), and innovative multimodal and multisensory stimulation training intervention (combined group). The Kubota water swallow test and functional oral intake scale (FOIS) were used to assess the effective improvement rate of feeding function. Differences in scores of modified Mann assessment of swallowing (MMASA), swallowing quality of life (SWAL-QOL), and National Institute of Health Stroke scale (NIHSS) among the three groups were compared before intervention, and at 4 and 8 weeks post-intervention. SPSS 27.0 software was used to analyze the data by one-way ANOVA, repeated measures ANOVA, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis. Results:(1) After 8 weeks of intervention, the effective improvement rates of feeding function were 75.00%(27/36) and 72.22%(26/36) in the stimulation group and rehabilitation group, respectively, which were both lower than that in the combined group (94.44%(34/36), both P<0.05). (2) The interaction effect between time and group was significant in MMASA scores among the three groups before and after intervention ( F=2.569, P<0.05). MMASA scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, MMASA scores in the combined group (85.64±11.26, 92.56±10.55) were higher than those in the stimulation group (73.52±12.65, 82.97±12.84) and rehabilitation group (72.47±11.38, 84.39±12.29) (all P<0.05). (3) The interaction effect between time and group was significant in SWAL-QOL total scores among the three groups before and after intervention ( F=18.561, P<0.05). SWAL-QOL total scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups ( P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, SWAL-QOL total scores in the combined group (115.64±9.26, 135.68±9.55) were higher than those in the stimulation group (108.42±8.65, 113.75±8.84) and rehabilitation group (108.37±8.38, 114.39±9.29) (all P<0.05). (4) The interaction effect between time and group was significant in NIHSS scores among the three groups before and after intervention ( F=7.890, P<0.05). NIHSS scores at 8 weeks post-intervention were lower than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also lower than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, NIHSS scores in the combined group (8.36±1.35, 5.22±1.05) were lower than those in the stimulation group (11.65±2.11, 8.78±1.12) and rehabilitation group (11.32±2.03, 8.36±1.17) (all P<0.05). Conclusion:Multimodal and multisensory stimulation training can improve feeding-swallowing function and neurological impairment in stroke patients with dysphagia, with intervention effects superior to those of either approach used alone.

Objective:To investigate the effect of triply periodic minimal surfaces (TPMS) structure and ceramic volume fraction on the mechanical properties of polymer-infiltrated ceramic network (PICN) composite and reveal its strengthening and toughening mechanism.Methods:In this study, TPMS structures with gyroid (G), primitive (P), diamond (D), and ceramic volume fraction (40%, 55%, 70%, 85%) were designed. Porous zirconia scaffolds were prepared using stereolithography technology, and resin was infiltrated into the scaffolds through a vacuum. Then, the PICN composites were obtained after curing. The bending strength, elastic modulus and fracture toughness of PICN were tested using an electronic universal testing machine, with commercial PICN as the control group. The micromorphology of PICN was observed through stereomicroscope and scanning electron microscope. The cytocompatibility of PICN was verified by using cell counting kit, live/dead cell staining and phalloidin staining.Results:The bending strength values of PICN with different ceramic volume fractions ranged from 82.0 MPa to 376.0 MPa, and they gradually increased as the ceramic volume fraction rised. The elastic modulus values of PICN with different ceramic volume fractions ranged from 12.1 GPa to 56.1 GPa. The fracture toughness values of PICN with different ceramic volume fractions ranged from 1.7 MPa·m 1/2 to 6.5 MPa·m 1/2. The bending strength of 85G PICN reached 306.0 MPa, and it had the highest fracture toughness (6.5 MPa·m 1/2) and an appropriate elastic modulus between that of the control group and that of enamel. Under scanning electron microscopy, it could be observed that the cracks branch and deflect at the interface and eventually terminate within the resin phase. After co-culture with PICN, the survival rate of mouse fibroblasts exceeded 80%, indicating that PICN had no cytotoxicity. Conclusions:The PICN composite with TPMS structure can satisfy the mechanical properties and cytocompatibility of dental prosthesis.

Aim To investigate the protective effect of Siwu decoction(SWD)on immune injury induced by 60Coγ-rays in mice and the related mechanism.Meth-ods C57BL/6J mice were randomly divided into six groups:Control group(Control),Model group(Mod-el),Siwu decoction low-dose group(SWD-L),Siwu decoction medium-dose group(SWD-M),Siwu decoc-tion high-dose group(SWD-H)and resveratrol positive group(Resveratrol,Res).The drug was continued to be administered 11 days before and after irradiation,with a single whole-body irradiation of 4 Gy,and all in-dexes were detected three days after irradiation.The changes of peripheral blood and organ indexes were de-tected.Serum levels of cytokine interferon gamma(IFN-γ),interleukin-1 β(IL-1 β),IL-2,IL-4,IL-6,IL-10,IL-17,transforming growth factor-β(TGF-β),tumor necrosis factor(TNF)-α,and immunoglobulin A(IgA),IgG,IgM,and complement protein 3(C3),C4 content were detected by enzyme-linked immunosorbent assay(ELISA).B lymphocytes,T lymphocytes,NK cells in spleen and T lymphocytes in thymus were de-tected by flow cytometry.The pathological changes of spleen and thymus were analyzed by hematoxylin-eosin(HE)staining.The expression of Sirt 1 protein in spleen after radiation was detected by immunofluores-cence staining.The protein contents of Sirt1,PI3K,Akt,p-Akt and mTOR in spleen were detected by Western blot assay.Results SWD could significantly increase LYMPH％and reduce pathological injury of spleen and thymus.Flow cytometry showed that SWD could significantly increase the percentage of CD19+B lymphocytes in spleen,decrease the percentage of NK lymphocytes and the ratio of CD4+/CD8+in spleen and thymus.ELISA results showed that SWD signifi-cantly inhibited the expression of IL-1 β,IL-2,IL-6,IL-17,IFN-γ,TGF-β,TNF-α,and increased the content of anti-inflammatory factors IL-4 and IL-10.At the same time,SWD significantly inhibited the increase of IgA,IgG,IgM,C3 and C4 induced by radiation.The results of immunofluorescence staining and Western blot showed that SWD could decrease the expression of PI3K,Akt,p-Akt and mTOR protein,and enhance the expression of Sirt1 protein.Conclusions SWD has obvious preventive effect on immune damage induced by 60Co gamma radiation in mice.The mechanism may be related to Sirt1-PI3K-Akt-mTOR.

Radical resection of mid-and low-rectal cancer requires not only oncologic safety but also preservation of organs and postoperative bowel function.While a 1-2 cm distal resection margin has been largely accepted,the optimal length of the proximal margin remains highly controversial.Clinically,the"10-cm rule"derived from colon cancer is often referenced,yet its applicability to rectal cancer lacks consistent supporting evidence.Previous studies have shown that an excessively long proximal margin may increase anastomotic tension and lead to anastomotic leakage,whereas insufficient resection heightens the risk of positive margins and local recurrence.In addition,the extent of lymph node metastasis,vascular perfusion of the proximal bowel,radiation-induced injury after neoadjuvant chemoradiotherapy,and postoperative bowel function-particularly low anterior resection syndrome-are all important factors influencing the selection of the proximal margin.In recent years,the application of indocyanine green fluorescence imaging has provided new evidence for intraoperative assessment of bowel perfusion;for patients receiving neoadjuvant chemoradiotherapy,radiation injury presents a gradient pattern,and resecting approximately≥20 cm proximal to the tumor may reduce the incidence of anastomosis-related complications.Based on current literature,this review provides a systematic overview of the historical evolution,influencing factors,and clinical evidence regarding proximal resection margins in rectal cancer surgery,with the aim of informing individualized margin selection and optimizing surgical strategies.

Objective:This study aims to improve the management level and quality of horizontal scientific research contracts in hospitals, reduce the risk of contract management, and explore an efficient mode of information management of horizontal scientific research contract management.Methods:Taking a Tertiary Grade A hospital as an example, this study described and summarized the management status of horizontal scientific research contracts from 2018 to 2022, sorted out the potential risks and prevention and control nodes of the review, signing, performance, and archiving of horizontal scientific research contracts in the whole cycle management process, and designed an information management model according to the relevant elements of risk prevention and control and the standardized requirements of contract management, thereby developing information platform related functions.Results:The horizontal research contract management function of the clinical research platform based on the integration concept was available to meet the requirements of risk prevention and control of horizontal research contracts, and the contract review and signing cycle of the information management mode was shortened by 33.33% and 31.95% respectively compared with the traditional management mode. The platform realized a standardized whole process management of contract submission, review, repair and revision, signing, performance, and filing.Conclusions:Information management can effectively reduce the risk of horizontal scientific research contract management. It is necessary to strengthen the docking and interaction function with other information platforms and further explore the information auxiliary function to improve the refined management effect of horizontal scientific research contracts.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To investigate the effects of multimodal and multisensory stimulation training on feeding-swallowing and neurological functions in stroke patients with dysphagia.Methods:Stroke patients with dysphagia treated at Henan Provincial People's Hospital from January 2023 to October 2024 were enrolled. Patients were randomly divided into three groups according to the random number table method, with 36 patients in each group. These three groups underwent different interventions for a period of 8 weeks: multisensory stimulation intervention (stimulation group), multimodal rehabilitation training intervention (rehabilitation group), and innovative multimodal and multisensory stimulation training intervention (combined group). The Kubota water swallow test and functional oral intake scale (FOIS) were used to assess the effective improvement rate of feeding function. Differences in scores of modified Mann assessment of swallowing (MMASA), swallowing quality of life (SWAL-QOL), and National Institute of Health Stroke scale (NIHSS) among the three groups were compared before intervention, and at 4 and 8 weeks post-intervention. SPSS 27.0 software was used to analyze the data by one-way ANOVA, repeated measures ANOVA, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis. Results:(1) After 8 weeks of intervention, the effective improvement rates of feeding function were 75.00%(27/36) and 72.22%(26/36) in the stimulation group and rehabilitation group, respectively, which were both lower than that in the combined group (94.44%(34/36), both P<0.05). (2) The interaction effect between time and group was significant in MMASA scores among the three groups before and after intervention ( F=2.569, P<0.05). MMASA scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, MMASA scores in the combined group (85.64±11.26, 92.56±10.55) were higher than those in the stimulation group (73.52±12.65, 82.97±12.84) and rehabilitation group (72.47±11.38, 84.39±12.29) (all P<0.05). (3) The interaction effect between time and group was significant in SWAL-QOL total scores among the three groups before and after intervention ( F=18.561, P<0.05). SWAL-QOL total scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups ( P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, SWAL-QOL total scores in the combined group (115.64±9.26, 135.68±9.55) were higher than those in the stimulation group (108.42±8.65, 113.75±8.84) and rehabilitation group (108.37±8.38, 114.39±9.29) (all P<0.05). (4) The interaction effect between time and group was significant in NIHSS scores among the three groups before and after intervention ( F=7.890, P<0.05). NIHSS scores at 8 weeks post-intervention were lower than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also lower than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, NIHSS scores in the combined group (8.36±1.35, 5.22±1.05) were lower than those in the stimulation group (11.65±2.11, 8.78±1.12) and rehabilitation group (11.32±2.03, 8.36±1.17) (all P<0.05). Conclusion:Multimodal and multisensory stimulation training can improve feeding-swallowing function and neurological impairment in stroke patients with dysphagia, with intervention effects superior to those of either approach used alone.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective: To explore the effect of different obesity indicators in predicting cardiovascular and cerebrovascular diseases (CVD) risk among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for the early identification of CVD risk among T2DM patients. Methods: The patients with T2DM under community management in Qingpu District, Shanghai Municipality were selected as the study subjects in January 2025. Basic information such as gender, age, and blood glucose control status were collected through the Shanghai Chronic Disease Information Management System, while history of CVD were obtained from residents' electronic health records and the Shanghai Disease Control Information Platform. Obesity was assessed using body mass index (BMI), waist circumference (WC), BMI combined with WC, waist-to-height ratio (WHtR), and triglyceride (TG) combined with WC indicators. The association between obesity and CVD was analyzed using multivariable logistic regression models. The predictive effect of each obesity indicators for CVD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 4 367 patients with T2DM were included, including 2 121 males (48.57%) and 2 246 females (51.43%). The average age was (68.71±8.05) years. The prevalence of CVD was 44.49%. Multivariable logistic regression analysis showed that after adjusting for age, education level, history of hypertension, duration of T2DM, use of glucose-lowering medications, renal function, and blood glucose control status, obese T2DM patients had a 389.4% increased risk of CVD compared to those with normal BMI; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WC; T2DM patients with isolated general obesity and compound obesity had 161.0% and 241.1% increased risks of CVD, respectively, compared to those with normal BMI and WC; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WHtR; T2DM patients with normal TG-high WC and high TG-high WC phenotypes had 83.1% and 68.8% increased risks of CVD, respectively, compared to those with normal TG and normal WC (all P<0.05). BMI had the highest AUC, at 0.714, with sensitivity and specificity of 0.675 and 0.642, respectively. This was followed by BMI combined with WC, which had an AUC of 0.707, with sensitivity and specificity of 0.635 and 0.679, respectively. Conclusions Obesity defined by BMI, WC, BMI combined with WC, WHtR, and TG combined with WC increases the risk of CVD among patients with T2DM. BMI and BMI combined with WC have better predictive effect in predicting CVD risk among patients with T2DM, and can be used as the primary obesity indicators for CVD risk screening.